Cecal vanishing tumor associated with cytomegalovirus infection in an immunocompetent elderly adult

Abstract

Gastrointestinal involvement in cytomegalovirus (CMV) infection is well documented among immunocompromised patients and is also observed in immunocompetent individuals. The presentation of this infection can sometimes mimic those of other diseases, thus making accurate diagnosis difficult. We herein report a rare case of an immunocompetent elderly adult with gastrointestinal CMV infection that presented as a vanishing tumor at the cecum. A 76-year old man initially presented with lower abdominal pain. Colonoscopy revealed a tumorous lesion with irregular ulceration observed at the ileocecal valve. Histological findings of a biopsy specimen revealed intranuclear inclusions which were positive for CMV on immunohistochemical staining. However, this tumorous lesion disappeared within 7 wk from the initial hospital visit without any further treatment. Inflammatory pseudotumors associated with CMV infection should be considered as a differential diagnosis of tumorous lesions in the colon, even in immunocompetent adults.

INTRODUCTION

Gastrointestinal involvement in cytomegalovirus (CMV) infection is well documented among immunocompromised patients. However, recent reports reveal its occurrence in immunocompetent individuals as well as with some instances of life-threatening manifestations, particularly in elderly adults with other comorbidities[1-3]. The clinical characteristics of this infection can sometimes mimic those of other diseases, making accurate diagnosis difficult[4]. Although most prototypical lesions present with well-defined punched-out ulceration, endoscopic findings of gastrointestinal CMV infection may present with various appearances such as erosion, ulceration, mucosal hemorrhage and stenosis[4]. Awareness of these characteristics and accurate diagnosis by histological examination are essential for antiviral therapy. In contrast, self-limited CMV infection in the absence of antiviral therapy is also reported in immunocompetent hosts[1,5].

We herein report a rare case of an immunocompetent elderly adult with gastrointestinal CMV infection that presented as a vanishing tumor at the ileocecal valve.

CASE REPORT

A 76-year old man initially presented with lower abdominal pain persisting over 4 d. Although he had a past history of cerebral infarction and hypertension, his general condition was good and his performance status was well maintained. Physical examination revealed tenderness in the right lower quadrant of the abdomen. Rebound tenderness was not detected. Laboratory investigations indicated increased white blood cell count (11 300 cells/mm³; normal range 3600-9200 cells/mm³), elevated C-reactive protein (9.53 mg/dL; normal range 0.70-1.17 mg/dL) and elevated γ-GTP levels (228 IU/L; normal range 12-73 IU/L). Serum creatinine levels (0.76mg/dl; normal range 0.70-1.17 mg/dL) were normal. Fasting plasma glucose levels (93 mg/dL; normal range 60-110 mg/dL) and hemoglobin A1c levels (5.2%; normal range 4.3%-5.8%) were normal. The levels of tumor markers, carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9), were normal while the level of soluble IL-2 receptor was slightly elevated (538 U/mL; normal range 145-519 U/mL). Other laboratory tests yielded normal results.

After initial clinical and laboratory evaluation, antibiotic therapy using ceftriaxone (CTRX) and levofloxacin (LVFX) for a probable diagnosis of acute appendicitis, diverticulitis or bacterial ileitis was initiated. His clinical condition improved gradually and the abdominal pain disappeared within a week. Two weeks later, a follow-up colonoscopy was performed. A tumorous lesion with irregular ulceration was observed at the ileocecal valve and multiple diverticula were also detected in the ascending colon and cecum (Figure 1). Abdominal computed tomography revealed an enhanced mass lesion of 2 cm diameter in the cecum (Figure 2). Histological findings of a biopsy specimen from the tumorous lesion revealed intranuclear inclusions. Immunohistochemical staining for CMV revealed scattered positive cells (Figure 3). Following pathological diagnosis, the patient tested negative for HIV, positive for antinuclear antibody (1:80), negative for anti-DNA antibody and complement activity (C3 and C4) was in the normal range. Because his abdominal symptoms disappeared and physical examination revealed no tenderness in the right lower quadrant of the abdomen, we performed an endoscopic examination by double balloon enteroscopy at 49 d after the initial hospital visit to re-evaluate the focal lesion for antiviral therapy and to distinguish it from a possible coexisting neoplasia, especially a lymphoma. However, the tumorous lesion at the ileocecal valve had vanished and both immunohistochemical staining for PCR and CMV from the biopsy sample were negative. We could not detect any other inflammatory or neoplastic lesion in the ileum and colon. Twelve months of follow-up observation later, the patient appears healthy with no evidence of recurrence of CMV colitis.

Figure 1.

Endoscopic findings of the tumorous lesion at the ileocecal valve. A: Tumorous lesion with a diameter of 2 cm is observed at the ileocecal valve and multiple diverticula are detected in the cecum; B: The tumorous lesion disappeared 30 d after initial examination without any antiviral therapy.

Figure 2.

Computed tomography scan revealed an enhanced mass lesion with a diameter of 2 cm in the cecum (indicated by an arrow).

Figure 3.

Histological findings of endoscopic forceps biopsy specimens. A:Hematoxylin-Eosin staining ×100; B: Immunohistochemical staining for cytomegalovirus reveals positive cells with inclusion.

DISCUSSION

CMV is a member of the herpes virus family and is a common pathogen with serology indicating prior exposure in 40%-100% of the general population[6]. Although human CMV infection can be seen at all stages of life, it often affects those who are immunosuppressed and can commonly cause retinitis, pneumonitis or enteritis in such patients[7]. CMV complications usually occur in advanced acquired immune deficiency syndrome when CD4 lymphocyte counts drop below 50 cells/mm³ and among transplant recipients as a reactivation of latent infection. Most primary CMV infections in immunologically healthy adults are asymptomatic or associated with a mild mononucleosis-like syndrome[7].

In the colonic manifestation of CMV infection, multiple erosions or ulcers are common and sometimes may cause perforation in severe cases[8]. However, rare manifestations of CMV infections of the colon include solitary mucosal ulcers, toxic megacolon[9], pseudomembrane formation[10,11] and ischemic colitis[12]. Isolated cases of pseudoneoplastic appearance of CMV colitis associated with polypoid masses or strictures have been documented in literature pertaining to HIV-positive patients[13] and HIV-negative patients[14-16]. Most of these cases involved surgical resection and/or antiviral therapy. However, this is the first report, as far as we could find, detailing the disappearance of a CMV-associated tumor in the absence of antiviral therapy.

In this case, the initial symptoms were similar to acute appendicitis, diverticulitis or bacterial ileitis, and laboratory data indicated successful management of inflammation by initial antibiotic therapy. Therefore, CMV colitis concomitant with pathogenic bacterial infection could be a possibility when the patient first visited our hospital. Several reports reveal that CMV secondarily colonizes bowel mucosa previously affected by another inflammatory process such as inflammatory bowel disease[17] and colitis with other pathogens[18,19]. CMV is also documented to behave nonpathogenically in some cases[4]. In this case, no evidence of inflammatory bowel disease or other types of colitis was detected in the histopathological examination.

In a meta-analysis of CMV colitis outcomes in immunocompetent hosts (44 cases), the rate of spontaneous remission was 31.8% but > 50% in patients younger than 55 years old. Death occurred in 31.8% patients older than 55 years old. Highest mortality rates were associated with immune-modulating conditions such as diabetes mellitus, renal failure and malignancies. Younger (< 55 years) and otherwise healthy patients were able to recover from CMV infection without antiviral therapy[1]. According to this meta-analysis, antiviral therapy with ganciclovir or foscarnet seems to be mandatory for older patients and for patients with immune-modulating conditions. Clinicopathological significance of CMV remains to be elucidated and might differ among individual cases.

In conclusion, we report a rare case of an immunocompetent elderly adult with a gastrointestinal CMV infection that showed a vanishing tumor at the ileocecal valve of the cecum. Inflammatory pseudotumors associated with CMV virus infection should be considered as differential diagnosis of tumorous lesion in the colon, even in immunocompetent hosts. This case certainly represents a clinical characteristic of CMV colitis in immunocompetent hosts. However, further clinical experience is required to clarify the need for antiviral therapy in an immunocompetent host.